Abstract
The fifth edition of Virulence Mechanisms of Bacterial Pathogens reviews classical and contemporary literature defining the drivers that establish the foundations of infectious disease. These drivers include transcriptional products and behavioral strategies that directly facilitate bacterial survival inside the host. Chapter 1 rightly initiates this review by defining the ongoing evolutionary battle between host and pathogen. It delineates the role natural selection plays in sustaining the cost-benefit outcome necessary for gene survival. Unlike other comments on bacterial survival due to evolution, however, the authors speak more to the temporal, epigenetic responses of gene activation and silencing than the trial and error of gene mutation. This is not to say that they consider mutation irrelevant. Rather, the authors seem to integrate the requirement for gene mutation with an argument that the complex molecular dance between host and pathogen influences species survival substantially more than any single stochastic mutation responding to the selective pressures of a new environment.
Subsequent chapters provide additional details about endogenous and exogenous drivers and the methods by which they regulate the infection process. The editors have established a recurring pattern defining how the many (bacterial and host-derived) molecular agonists and antagonists are involved in the establishment of infection. The chapter topics and their sequencing present a logical framework for a reader to appreciate the strategies bacteria employ to compete at the cellular level. The editors, for example, appear to have used genetics, biochemistry, and molecular interactions of bacteria, while unique for a given virulence factor, as interchapter themes to direct the reader’s attention to their role in pathogen entry, niche fulfillment, resource acquisition, detection avoidance, and replication. Importantly, the text also reflects the impact of host responses that lead to either pathogen death and expulsion or reluctant permission for community living. A number of chapters also speak to the use of computer modeling to predict and comment on these mechanisms of host-pathogen negotiations. In a nod to the worldwide microbiome and metagenomic projects, the book integrates data across chapters that report on various “omic” responses during the infection process.
The text further updates the reader on classical virulence factors and augments biochemical mechanisms with data reflecting an influence of biotic (eg, host cells, fungi, other bacteria) and/or abiotic (eg, surfaces, lipids, peptides, neurochemicals) components that, in turn, govern pathogen survival. Chapter 4, for example, describes the processes of quorum sensing and biofilm development as social interactions, which facilitate evolutionary modifications. Here, the authors comment on how the loss of genes directing anabolic or catabolic pathways may change bacterial social/behavioral actions (eg, creating cheater behavior) and thus prevent extinction of that clone. In addition, the loss of the type VI secretion system (T6SS) also disrupts biofilm formation of several species of bacteria, notably the pathogenic Escherichia coli, altering their fitness for survival (Chapter 12). In Chapter 19, the authors focus on specific gene control of in vitro biofilm development in the staphylococci and emphasize the importance of environmental conditions that can direct in vivo expression of staphylococcal genes. Adhesins and other cell surface proteins are considered in biofilm development, with specific attention given to those that bind host molecules (eg, fibrinogen, cytokeratin) and/or synthetic materials. The authors clearly convey that in vitro conditions, which influence biofilm integrity, are not always predictive of biofilm development in vivo.
Chapters 8 through 13 provide considerable data on the structure and function of the various protein secretion mechanisms of bacteria (except the T7 S). Examples of bacteria incorporating specific protein transfer systems and how they are used for infection are detailed. The gene expression and molecular assembly of each are presented so as to differentiate the respective roles of protein (and nucleic acid) shuttling for viability vs virulence. Other chapters comment on pathogen use of structural components as virulence factors. Research reported from within various chapters, for example, defines how small RNA (sRNA) form riboswitches, thermosensors, quorum sensing controllers, and more. Furthermore, authors report data from global transcriptome studies demonstrating an increased and diversified sRNA output affecting gene regulation (Chapter 7). The authors of Chapter 22 detail the role of lipids and their microdomains as they facilitate bacterial entry into host cells, are enzymatically targeted to promote escape of intracellular bacteria, are incorporated into various pathogen structures, or are metabolized to create second messengers or for energy.
Mechanisms of bacterial survival, in response to environmental stressors, are reviewed in Chapters 20, 21, and 23. Here the processes of dormancy, biofilm development, metabolic and morphology control, and sporulation are detailed. The remaining chapters primarily focus on the defensive virulence mechanisms that pathogens have evolved to survive inside a multicellular host and the therapies that have been used to target bacteria and their virulence mechanisms. Bacterial strategies include methods to (1) evade pH and osmolality shifts, as well as oxidative and nitrosative species (Chapters 14 and 21); (2) overcome the effects of antimicrobial peptides (Chapter 15); (3) use antigenic variation (Chapter 16); and (4) resist antibiotics (Chapter 17). Each chapter provides an informative review of the literature and offers comment on modification of current therapies to further defeat the infection process. Last, adhesion (Chapter 27), drug resistance (Chapter 26), and specific ecology modifications and metabolic pathway interruption (Chapters 28 and 29) are explained historically and with a nod to future permutation in the ongoing battle to treat infection.
Virulence Mechanisms of Pathogenic Bacteria is divided into 7 sections (29 chapters with color figures): bacterial-host interface, bacterial communication and virulence, bacterial secretion systems, bacterial defenses, bacterial persistence (within and between hosts), host cell enslavement by intracellular bacteria, and targeted therapies. It has 73 contributors. In all, the editors have assembled a solid team of authors who have constructed a thorough and logically presented reference tool. The book is well organized, providing a current synopsis of the primary virulence mechanisms used by bacteria to establish infection and consideration of the various methods that may overcome the infectious disease process.